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A Study of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-invasive Bladder Cancer (MIBC) of the Bladder

NCT04658862

Description:

The purpose of study is to compare bladder intact-event free survival (BI-EFS) in participants receiving TAR-200 in combination with cetrelimab versus concurrent chemoradiotherapy.

Related Conditions:
  • Bladder Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-invasive Bladder Cancer (MIBC) of the Bladder
  • Official Title: A Phase 3, Multi-center, Randomized Study Evaluating Efficacy of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-Invasive Urothelial Carcinoma (MIBC) of the Bladder Who Are Not Receiving Radical Cystectomy

Clinical Trial IDs

  • ORG STUDY ID: CR108917
  • SECONDARY ID: 2020-002620-36
  • SECONDARY ID: 17000139BLC3001
  • NCT ID: NCT04658862

Conditions

  • Urinary Bladder Neoplasms

Interventions

DrugSynonymsArms
CetrelimabJNJ-63723283TAR-200 + Cetrelimab
TAR-200JNJ-17000139TAR-200 + Cetrelimab
CisplatinChemotherapy (cisplatin or gemcitabine) + Radiation Therapy
GemcitabineChemotherapy (cisplatin or gemcitabine) + Radiation Therapy

Purpose

The purpose of study is to compare bladder intact-event free survival (BI-EFS) in participants receiving TAR-200 in combination with cetrelimab versus concurrent chemoradiotherapy.

Detailed Description

      TAR-200 is a gemcitabine intravesical delivery system that provides a continuous release of
      gemcitabine into the urine. Urothelial carcinoma, specifically transitional cell carcinoma of
      the upper and lower genitourinary tract, has demonstrated meaningful responsiveness to
      deoxycytidine analogues. Gemcitabine has also demonstrated efficacy and a tolerable safety
      profile in NMIBC and metastatic urothelial carcinoma. Study consists of screening phase of 42
      days, treatment phase and follow up phase. The total duration of study will be up to 8 years.
      Efficacy evaluation includes disease assessment (Cystoscopy/TURBT Biopsy/Pathology) and
      Patient Reported Outcomes (Quality of Life Assessments) and safety assessments includes vital
      sign measurements, 12-lead electrocardiogram (ECG), physical examinations, clinical
      laboratory tests, cystoscopic examination, anti-drug antibody (ADA) assessments, concomitant
      treatments/procedures and adverse event monitoring.
    

Trial Arms

NameTypeDescriptionInterventions
TAR-200 + CetrelimabExperimentalParticipants will receive intravesical TAR-200 every 3 weeks (21 days indwelling) for first 18 weeks and thereafter from Week 24 every 12 weeks through study Year 3 in combination with Cetrelimab.
  • Cetrelimab
  • TAR-200
Chemotherapy (cisplatin or gemcitabine) + Radiation TherapyActive ComparatorParticipants will receive chemotherapy based on investigator's choice from either cisplatin intravenously once weekly for 6 weeks or gemcitabine intravenously twice weekly for 6 weeks as Standard of Care (SOC) along with radiation therapy from either conventional radiotherapy (64 Gray [Gy], bladder only) for up to 6.5 weeks or hypo-fractionated radiotherapy (55 Gy, bladder only) for up to 4 weeks.
  • Cisplatin
  • Gemcitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Ineligible for or have elected not to undergo radical cystectomy

          -  All adverse events associated with any prior surgery and/or intravesical therapy must
             have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
             Grade less than (<) 2 prior to randomization

          -  Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2

          -  Thyroid function tests within normal range or stable on hormone supplementation per
             investigator assessment.

          -  Adequate bone marrow, liver, and renal function: Bone marrow function (without the
             support of cytokines or erythropoiesis-stimulating agent in preceding two weeks):
             Absolute neutrophil count (ANC) greater than or equal to (>=) 1,000/cubic millimeters
             (mm^3); Platelet count >=75,000/mm^3; Hemoglobin >=8.0 grams per deciliter (g/dL);
             Liver function: (Total bilirubin less than or equal to (<=) 1.5 * upper limit of
             normal (ULN) or direct bilirubin <= ULN for participants with total bilirubin levels
             greater than (>)1.5*ULN (except participants with Gilbert's Syndrome, who must have a
             total bilirubin < 3.0 mg/dL), and Alanine aminotransferase (ALT) and aspartate
             aminotransferase (AST) less than or equal to (<=) 2.5* institutional ULN); Renal
             function: Creatinine clearance >40 mL/min either directly measured via 24-hour urine
             collection, calculation using the Cockcroft-Gault formula, or calculation for the
             modification of diet in renal disease for adult participants

        Exclusion Criteria:

          -  Must not have had urothelial carcinoma or histological variant at any site outside of
             the urinary bladder. Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract
             (including renal pelvis and ureter) is allowable if treated with complete
             nephrouretrectomy within 24 months

          -  Must not have diffuse CIS based on cystoscopy and biopsy. Diffuse, or multi-focal, CIS
             is defined as the presence of at least 4 distinct CIS lesions in the bladder at the
             time of the Screening re-TURBT

          -  Participants must not have evidence of cT4b, or N1-3, or M1 disease based on local
             radiology staging (chest, abdomen, and pelvis must be performed using Computed
             tomography [CT] or Magnetic resonance imaging [MRI]) within 42 days prior to
             randomization

          -  Presence of any bladder or urethral anatomic feature that, in the opinion of the
             investigator, may prevent the safe placement, indwelling use, or removal of TAR 200

          -  Evidence of bladder perforation during diagnostic cystoscopy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time from Randomization to the First Bladder Intact Event-free Survival (BI-EFS) event
Time Frame:Up to 8 years
Safety Issue:
Description:Time from randomization to the first BI-EFS event includes histologically proven presence of muscle-invasive bladder cancer (MIBC), clinical evidence of nodal or metastatic disease (as assessed by RECIST 1.1 criteria), radical cystectomy (RC), or death due to any cause.

Secondary Outcome Measures

Measure:Metastasis-free survival (MFS)
Time Frame:Up to 8 years
Safety Issue:
Description:MFS is measured from time from randomization to first radiologic (as assessed by RECIST 1.1 criteria) or histologic evidence of metastatic disease or death due to any cause.
Measure:Overall Survival (OS)
Time Frame:Up to 8 years
Safety Issue:
Description:OS is defined as time from randomization to death.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 8 years
Safety Issue:
Description:ORR is defined as proportion of participants who have complete response (CR) (defined as Negative biopsy, and Computed tomography/Magnetic resonance imaging [CT/MRI] of chest, abdomen, and pelvis showing no evidence of local recurrence, progression, or metastatic disease) or partial response (PR): (defined as down staging: biopsy proven non-invasive disease less than [<] T1 and CT/MRI of chest, abdomen, and pelvis showing no evidence of metastatic disease) or non-response (those not achieving a complete response or down-staging, or those who do not undergo a biopsy will be considered non-responders).
Measure:Number of Participants with Adverse Events (AEs) According to Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame:Up to 8 years
Safety Issue:
Description:Number of Participants with AEs by Severity as assessed by CTCAE version 5 will be reported. Grade refers to the severity of the AE as follows: Grade 1- Mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2- Moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental Activities of Daily Living (ADL); Grade 3- Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care ADL; Grade 4- Life-threatening consequences, urgent intervention indicated; Grade 5- Death related to AE.
Measure:Number of Participants with AEs by Severity according to Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)
Time Frame:Up to 8 years
Safety Issue:
Description:NCI PRO-CTCAE is a patient-reported outcome measure used to evaluate symptomatic toxicity in participants on cancer clinical trials. The NCI PRO-CTCAE is an item bank. The items selected for this study include all NCI PRO-CTCAE gastrointestinal items and urinary items. These items include taste changes, decreased appetite, nausea, vomiting, heartburn, gas, bloating, hiccups, constipation, diarrhea, abdominal pain, fecal incontinence, painful, urination, urinary urgency, urinary frequency, change in usual urine color, and urinary incontinence.
Measure:Number of Participants with Clinical Laboratory Abnormalities
Time Frame:Up to 8 years
Safety Issue:
Description:Number of participants with clinical laboratory abnormalities will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.
Measure:Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time Frame:From Baseline up to 8 years
Safety Issue:
Description:Change from baseline in systolic and diastolic blood pressure over time will be assessed.
Measure:Change From Baseline in Heart Rate
Time Frame:From Baseline up to 8 years
Safety Issue:
Description:Change from baseline in heart rate over time will be assessed.
Measure:Change from Baseline in Temperature
Time Frame:From Baseline up to 8 years
Safety Issue:
Description:Change from baseline in temperature over time will be assessed.
Measure:Safety Assessment by Changes From Baseline in Physical Examinations
Time Frame:From Baseline up to 8 years
Safety Issue:
Description:Physical examination which will be comprised of an examination of head, ears, eyes, nose, throat and neck, cardiovascular, respiratory, abdomen, musculoskeletal, skin, and genitourinary systems as assessed as normal or abnormal. A change from normal to abnormal or abnormal to normal, will be registered as a change from baseline.
Measure:Change from Baseline in Performance Status as assessed by Eastern Cooperative Oncology Group (ECOG) Scale
Time Frame:From baseline up to 8 years
Safety Issue:
Description:Change from baseline in performance status will be assessed by ECOG scale, where Grade 0 (fully active), Grade 1 (restricted in physically strenuous activity), Grade 2 (ambulatory and capable of all self-care), Grade 3 (capable of only limited self-care), Grade 4 (completely disabled), and Grade 5 (dead).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

April 2, 2021